Potent triazolinone-based angiotensin II receptor antagonists with equivalent affinity for both the AT1 and AT2 subtypes ☆

A series of subnanomolar (IC50 triazolinone-based AT1/AT2-balanced AII antagonists has been identified. The 70-240-fold gain in AT2 activity relative to prototype compounds was achieved by the introduction of a 5-acylamino group on the N2-aryl moiety and the addition of (3-F-5'-Pr)biphenyl substituents on 4. These analogues exhibited AT2/AT1 IC50 rations of ≤1 in multiple assay systems including human adrenal.